Dioscin ameliorates inflammatory bowel disease by up-regulating miR-125a-5p to regulate macrophage polarization.

Abstract

PURPOSE:

Dioscin has been proven to have anti-cancer, anti-inflammatory, and anti-infection roles. However, the role of Dioscin in inflammatory bowel disease (IBD) and its related mechanisms is unclear and needs further study.

METHODS:

The colitis model in mice was established. After Dioscin (20, 40, or 80 mg/kg) treatment, the colon length was measured by a ruler. Histopathology, inflammatory cytokines, gut permeability, tight junction proteins, macrophage infiltration, macrophage polarization, and miR-125a-5p level were detected by hematoxylin-eosin staining, enzyme-linked immunosorbent assay, quantitative real-time polymerase chain reaction (qRT-PCR), FITC-dextran, Western blot, and flow cytometry. In vitro experiments, after RAW264.7 cells induced by lipopolysaccharide (LPS)/interleukin-4 (IL-4), were treated with Dioscin and miR-125a-5p inhibitor, miR-125a-5p level, cell vitality, inflammatory cytokines, and M1/M2 marker genes were measured by qRT-PCR and MTT assay.

RESULTS:

Dioscin (20, 40, or 80 mg/kg) relieved DSS-triggered colitis and restrained the serum and colon of pro-inflammatory cytokines expression. Meanwhile, different concentrations' Dioscin weakened M1 macrophage polarization but facilitated tight junction protein expressions, M2 macrophage polarization, and miR-125a-5p level in colitic mice. Moreover, miR-125a-5p inhibitor reversed the modulation of Dioscin on miR-125a-5p expression, cell vitality, and inflammatory cytokines in lipopolysaccharide (LPS)-induced RAW264.7 cells. We further discovered that Dioscin restrained M1 marker gene (CD16) expression while intensifying M2 marker genes (CD206 and Arginase-1) expressions in vitro, which was reversed by miR-125a-5p inhibitor.

CONCLUSION:

Dioscin modulated macrophage polarization by increasing miR-125a-5p, thereby improving the intestinal epithelial barrier function and reducing IBD.

• Authors: Lingyan Shi, Peichen Zhang, Ruifang Jin, Xiaowei Chen, Lemei Dong, Weichang Chen
• Journal: Journal of clinical laboratory analysis (J Clin Lab Anal) Vol. 36 Issue 6 Pg. e24455 (Jun 2022) ISSN: 1098-2825 [Electronic] United States
• PMID: 35524480 (Publication Type: Journal Article)
• Copyright: © 2022 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals LLC.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Lipopolysaccharides
• MicroRNAs
• dioscin
• Diosgenin

Topics

• Animals
• Anti-Inflammatory Agents (metabolism)
• Colitis (chemically induced, metabolism)
• Cytokines (metabolism)
• Diosgenin (analogs & derivatives)
• Humans
• Inflammatory Bowel Diseases (drug therapy, genetics)
• Lipopolysaccharides (pharmacology)
• Macrophages (metabolism)
• Mice
• MicroRNAs (genetics, metabolism)